Hyperaldosteronism is a medical condition characterized by excessive production of the hormone aldosterone. The adrenal glands produce aldosterone as part of the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure and water (fluid) balance. Within the RAAS, aldosterone causes the tubules of the kidneys to increase the reabsorption of ions (e.g., sodium) and water into the blood, which, in turn, increases blood volume and blood pressure. Accordingly, hyperaldosteronism is typically associated with hypertension. Even in the absence of hypertension, however, hyperaldosteronism can increase the risk of cardiac injury (including ischemic and fibrotic injury), left ventricular hypertrophy, stroke, and acute coronary syndromes. Hyperaldosteronism can be caused by adrenal conditions (e.g., adrenal adenoma, adrenal hyperplasia, and adrenal carcinoma, among others) or by overactivity of the RAAS. Conventional treatments include medications, e.g., renal competitive aldosterone antagonists, calcium channel blockers, angiotensin-converting-enzyme inhibitors, and angiotensin receptor blockers. These medications are not effective in all patients and typically have undesirable side effects. Conventional surgical approaches to treating hyperaldosteronism, such as adrenalectomy, can have serious complications. Accordingly, there is a need for alternative treatments.
The sympathetic nervous system (SNS) is a primarily involuntary bodily control system typically associated with stress responses. Fibers of the SNS extend through tissue in almost every organ system of the human body. For example, some fibers extend from the brain, intertwine along the aorta, and branch out to various organs. As groups of fibers approach specific organs, fibers particular to the organs can separate from the groups. Signals sent via these and other fibers can affect characteristics such as pupil diameter, gut motility, and urinary output. Such regulation can have adaptive utility in maintaining homeostasis or in preparing the body for rapid response to environmental factors. Chronic activation of the SNS, however, is a common maladaptive response that can drive the progression of many disease states. Excessive activation of the renal SNS in particular has been identified experimentally and in humans as a likely contributor to the complex pathophysiology of hypertension, states of volume overload (such as heart failure), and progressive renal disease. As examples, radiotracer dilution has demonstrated increased renal norepinephrine (NE) spillover rates in patients with essential hypertension.
Sympathetic nerves of the kidneys terminate in the blood vessels, the juxtaglomerular apparatus, and the renal tubules. Stimulation of the renal sympathetic nerves can cause increased renin release, increased sodium (Na+) reabsorption, and a reduction of renal blood flow. These neural regulation components of renal function are considerably stimulated in disease states characterized by heightened sympathetic tone as well as likely contribute to increased blood pressure in hypertensive patients. The reduction of renal blood flow and glomerular filtration rate as a result of renal sympathetic efferent stimulation is likely a cornerstone of the loss of renal function in cardio-renal syndrome (i.e., renal dysfunction as a progressive complication of chronic heart failure). Pharmacologic strategies to thwart the consequences of renal efferent sympathetic stimulation include centrally acting sympatholytic drugs, beta blockers (intended to reduce renin release), angiotensin converting enzyme inhibitors and receptor blockers (intended to block the action of angiotensin II calcium channel blockers), vasodilators (to counteract peripheral vasoconstriction caused by increased sympathetic drive), aldosterone blockers (to block the actions of increased aldosterone released from activation of the RAAS and aldosterone activation consequent to renin release), and diuretics (intended to counter the renal sympathetic mediated sodium and water retention). These pharmacologic strategies, however, have significant limitations including limited efficacy, compliance issues, side effects, and others.